McClure M W, Berkowitz S D, Sparapani R, Tuttle R, Kleiman N S, Berdan L G, Lincoff A M, Deckers J, Diaz R, Karsch K R, Gretler D, Kitt M, Simoons M, Topol E J, Califf R M, Harrington R A
Duke Clinical Research Institute, Durham, NC 27705, USA.
Circulation. 1999 Jun 8;99(22):2892-900. doi: 10.1161/01.cir.99.22.2892.
The significance of thrombocytopenia in patients experiencing an acute coronary syndrome (ACS) has not been examined systematically. We evaluated this condition in a large non-ST-elevation ACS clinical trial, with particular interest paid to its correlation with clinical outcomes.
Patients presenting without persistent ST elevation during an ACS were randomized to receive a double-blind infusion of the platelet glycoprotein (GP) IIb/IIIa inhibitor eptifibatide or placebo in addition to other standard therapies including heparin and aspirin. The primary end point was death/nonfatal myocardial infarction (MI) at 30 days, whereas bleeding and stroke were the main safety outcomes. Thrombocytopenia (nadir platelet count <100x10(9)/L or <50% of baseline) occurred in 7.0% of enrolled patients. The time to onset was a median of 4 days in both treatment arms. Patients with thrombocytopenia were older, weighed less, were more likely nonwhite, and had more cardiac risk factors. These patients experienced significantly more bleeding events: they were more than twice as likely to experience moderate/severe bleeding after adjustment for confounders. Univariably, ischemic events (stroke, MI, and death) occurred significantly (P<0.001) more frequently in patients with thrombocytopenia; multivariable regression modeling preserved this association with death/nonfatal MI at 30 days. Neither the use of heparin or eptifibatide was found to independently increase thrombocytopenic risk.
Although causality between thrombocytopenia and adverse clinical events could not be established definitively, thrombocytopenia was highly correlated with both bleeding and ischemic events, and the presence of this condition identified a more-at-risk patient population.
急性冠状动脉综合征(ACS)患者血小板减少的意义尚未得到系统研究。我们在一项大型非ST段抬高型ACS临床试验中评估了这种情况,特别关注其与临床结局的相关性。
在ACS期间无持续性ST段抬高的患者被随机分组,除接受包括肝素和阿司匹林在内的其他标准治疗外,还接受血小板糖蛋白(GP)IIb/IIIa抑制剂依替巴肽或安慰剂的双盲输注。主要终点是30天时的死亡/非致死性心肌梗死(MI),而出血和卒中是主要的安全性结局。7.0%的入选患者出现血小板减少(最低血小板计数<100×10⁹/L或<基线的50%)。两个治疗组的发病时间中位数均为4天。血小板减少的患者年龄更大、体重更轻、非白人的可能性更高,且有更多的心脏危险因素。这些患者发生的出血事件明显更多:在对混杂因素进行调整后,他们发生中度/重度出血的可能性是其他人的两倍多。单因素分析显示,血小板减少的患者发生缺血性事件(卒中、MI和死亡)的频率显著更高(P<0.001);多变量回归模型显示这种相关性在30天时与死亡/非致死性MI仍然存在。未发现使用肝素或依替巴肽会独立增加血小板减少风险。
虽然不能明确确定血小板减少与不良临床事件之间的因果关系,但血小板减少与出血和缺血性事件均高度相关,且这种情况的存在确定了一个风险更高的患者群体。